IP Library Granted Patent US 12,410,195
Granted Patent B2
US 12,410,195 · App. 18/741,739 · Granted Sep 9, 2025

Pharmaceutical compositions comprising 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)phenyl)butan-1-one for treating conditions of the central nervous system and cardiac disorders

Inventors: Peng Li (New Milford, NJ); Robert E Davis (San Diego, CA); Kimberly Vanover (New York, NY)
Assignee: INTRA-CELLULAR THERAPIES, INC.
C07D519/00
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Quick Facts
Patent No.
US 12,410,195
App. No.
18/741,739
Granted
Sep 9, 2025
Kind
B2
Abstract

The invention relates to pharmaceutical compositions comprising the compound of Formula I, and new methods and uses pertaining thereto, and pharmaceutical compositions thereof, such as methods of use in the treatment of diseases involving the 5-HT receptor, the serotonin transporter (SERT), and/or pathways involving dopamine D 2 receptor signaling, sodium channel activity, and/or norepinephrine transporter activity.

Claims (60)

1. A pharmaceutical composition comprising:

(i) a compound of Formula I:

in free base or pharmaceutically acceptable salt form; and

(ii) a compound of Formula II:

in free base or pharmaceutically acceptable salt form.

2. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises the compound of Formula I and the compound of Formula II in a weight ratio in the range of from 1:200 to 1:2000.

3. The pharmaceutical composition according to claim 2 , wherein the pharmaceutical composition comprises the compound of Formula I and the compound of Formula II in a weight ratio in the range of from 1:245 to 1:1000.

4. The pharmaceutical composition according to claim 2 , wherein the pharmaceutical composition comprises the compound of Formula I and the compound of Formula II in a weight ratio in the range of from 1:250 to 1:550.

5. The pharmaceutical composition according to claim 2 , wherein the pharmaceutical composition comprises the compound of Formula I and the compound of Formula II in a weight ratio in the range of from 1:300 to 1:500.

6. The pharmaceutical composition according to claim 2 , wherein the pharmaceutical composition comprises the compound of Formula I and the compound of Formula II in a weight ratio in the range of from 1:285 to 1:460.

7. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a tablet or a capsule.

8. The pharmaceutical composition according to claim 7 , wherein the compound of Formula II is in toluenesulfonic acid addition salt form.

9. The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition further comprises at least one pharmaceutically acceptable diluent or carrier in admixture with the compound of Formula I and the compound of Formula II.

10. The pharmaceutical composition according to claim 9 , wherein the pharmaceutically acceptable diluent or carrier is selected from the group consisting of (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k), (l), (m), (n), (o), (p), (q), (r), (s), (t), and (u):

(a) an anti-oxidant;

(b) a binder;

(c) a buffer;

(d) a colorant;

(e) a desiccant;

(f) a diluent;

(g) a disintegrant;

(h) a drying agent;

(i) a dye;

(j) an effervescent;

(k) a filler;

(l) a flavor;

(m) a glidant;

(n) a humectant;

(o) a lubricant;

(p) a plasticizer;

(q) a polymer;

(r) a surfactant;

(s) a sweetener;

(t) a thickening agent; and

(u) a wetting agent,

or a combination thereof.

11. The pharmaceutical composition according to claim 10 , wherein the pharmaceutically acceptable diluent or carrier is selected from the group consisting of (a), (b), (f), (g), (k), (m), (o), (s), and (t):

(a) an anti-oxidant;

(b) a binder;

(f) a diluent;

(g) a disintegrant;

(k) a filler;

(m) a glidant;

(o) a lubricant;

(s) a sweetener; and

(t) a thickening agent,

or a combination thereof.

12. The pharmaceutical composition according to claim 10 , wherein (a) the anti-oxidant is selected from the group consisting of ascorbic acid, butylated hydroxytoluene (BHT), citric acid, propyl gallate, and sodium metabisulfite.

13. The pharmaceutical composition according to claim 10 , wherein (b) the binder is selected from the group consisting of copovidone, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose.

14. The pharmaceutical composition according to claim 10 , wherein (f) the diluent or (k) the filler is selected from the group consisting of cellulose, dicalcium phosphate, isomalt, lactose monohydrate, and mannitol.

15. The pharmaceutical composition according to claim 14 , wherein the cellulose is microcrystalline cellulose.

16. The pharmaceutical composition according to claim 15 , wherein the microcrystalline cellulose is silicified microcrystalline cellulose.

17. The pharmaceutical composition according to claim 10 , wherein (g) the disintegrant is selected from the group consisting of croscarmellose sodium, crospovidone, and sodium starch glycolate.

18. The pharmaceutical composition according to claim 10 , wherein (m) the glidant is silicon dioxide or talc.

19. The pharmaceutical composition according to claim 10 , wherein (o) the humectant is glyceryl monostearate or magnesium stearate.

20. The pharmaceutical composition according to claim 10 , wherein the pharmaceutical composition comprises croscarmellose sodium and mannitol.

21. The pharmaceutical composition according to claim 10 , wherein the pharmaceutical composition comprises magnesium stearate and talc.

22. The pharmaceutical composition according to claim 10 , wherein the pharmaceutical composition comprises croscarmellose sodium, mannitol, and magnesium stearate.

23. The pharmaceutical composition according to claim 10 , wherein the pharmaceutical composition comprises croscarmellose sodium, mannitol, and talc.

24. The pharmaceutical composition according to claim 10 , wherein the pharmaceutical composition comprises croscarmellose sodium, mannitol, magnesium stearate, and talc.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 30, 2024
From: LI, PENG; DAVIS, ROBERT E.; VANOVER, KIMBERLY
To: INTRA-CELLULAR THERAPIES, INC.
Reel/Frame 068127/0932 →
Continuity (4)
Continuation 18240951 · Aug 31, 2023
Continuation 17757212
Provisional Application 62946568 · Dec 11, 2019
Related Publication 20240327436A1 · Oct 3, 2024
References Cited (186)
US 3299078A · Pachter · 1967 [cited by applicant]
US 3813392A · Sellstedt · 1974 [cited by applicant]
US 4001263A · Plattner et al. · 1977 [cited by applicant]
US 4238607A · Rajagopalan · 1980 [cited by applicant]
US 4389330A · Tice et al. · 1983 [cited by applicant]
US 4522944A · Doria et al. · 1985 [cited by applicant]
US 4530840A · Tice et al. · 1985 [cited by applicant]
US 4767628A · Hutchinson · 1988 [cited by applicant]
US 5004602A · Hutchinson · 1991 [cited by applicant]
US 5114976A · Norden · 1992 [cited by applicant]
US 5151419A · Perenyi et al. · 1992 [cited by applicant]
US 5538739A · Bodmer et al. · 1996 [cited by applicant]
US 6407092B1 · Hester et al. · 2002 [cited by applicant]
US 6544559B2 · Mesens et al. · 2003 [cited by applicant]
US 6548493B1 · Robichaud et al. · 2003 [cited by applicant]
US 6552017B1 · Robichaud et al. · 2003 [cited by applicant]
US 6699852B2 · Robichaud et al. · 2004 [cited by applicant]
US 6713471B1 · Robichaud et al. · 2004 [cited by applicant]
US 6849619B2 · Robichaud et al. · 2005 [cited by applicant]
US 6849640B2 · Ennis et al. · 2005 [cited by applicant]
US 7071186B2 · Robichaud et al. · 2006 [cited by applicant]
US 7081455B2 · Robichaud et al. · 2006 [cited by applicant]
US 7109339B2 · Lee et al. · 2006 [cited by applicant]
US 7183282B2 · Robichaud et al. · 2007 [cited by applicant]
US RE39679E · Robichaud et al. · 2007 [cited by applicant]
US RE39680E · Robichaud et al. · 2007 [cited by applicant]
US 7238690B2 · Robichaud et al. · 2007 [cited by applicant]
US 7375226B2 · Jolidon et al. · 2008 [cited by applicant]
US 7592454B2 · Lee et al. · 2009 [cited by applicant]
US 7645752B2 · McDevitt et al. · 2010 [cited by applicant]
US 8309722B2 · Tomesch et al. · 2012 [cited by applicant]
US 8598119B2 · Mates et al. · 2013 [cited by applicant]
US 8648077B2 · Tomesch et al. · 2014 [cited by applicant]
US 8779139B2 · Tomesch et al. · 2014 [cited by applicant]
US 8993572B2 · Mates et al. · 2015 [cited by applicant]
US 9161061B2 · Mesh-Iliescu et al. · 2015 [cited by applicant]
US 9168258B2 · Mates et al. · 2015 [cited by applicant]
US 9199995B2 · Tomesch et al. · 2015 [cited by applicant]
US 9315504B2 · Tomesch et al. · 2016 [cited by applicant]
US 9371324B2 · Mates et al. · 2016 [cited by applicant]
US 9393192B2 · Yam et al. · 2016 [cited by applicant]
US 9428506B2 · Mates et al. · 2016 [cited by applicant]
US 9586960B2 · Tomesch et al. · 2017 [cited by applicant]
US 9616061B2 · Mates et al. · 2017 [cited by applicant]
US 9708322B2 · Li et al. · 2017 [cited by applicant]
US 9745300B2 · Mates et al. · 2017 [cited by applicant]
US 9751883B2 · Tomesch et al. · 2017 [cited by applicant]
US 9956227B2 · Vanover et al. · 2018 [cited by applicant]
US 10072010B2 · Li et al. · 2018 [cited by applicant]
US 10077267B2 · Mates et al. · 2018 [cited by applicant]
US 10117867B2 · Mates et al. · 2018 [cited by applicant]
US 10221176B2 · Tomesch et al. · 2019 [cited by applicant]
US 10245260B2 · Yao et al. · 2019 [cited by applicant]
US 10322134B2 · Vanover et al. · 2019 [cited by applicant]
US 10464938B2 · Tomesch et al. · 2019 [cited by applicant]
US 10472359B2 · Li et al. · 2019 [cited by applicant]
US 10597394B2 · Mates et al. · 2020 [cited by applicant]
US 10597395B2 · Tomesch et al. · 2020 [cited by applicant]
US 10654854B2 · Li et al. · 2020 [cited by applicant]
US 10688097B2 · Yao et al. · 2020 [cited by applicant]
US 10702522B2 · Mates et al. · 2020 [cited by applicant]
US 10716786B2 · Li et al. · 2020 [cited by applicant]
US 10799500B2 · Yao et al. · 2020 [cited by applicant]
US 10844061B2 · Li et al. · 2020 [cited by applicant]
US 10899762B2 · Mates et al. · 2021 [cited by applicant]
US 10906906B2 · Li et al. · 2021 [cited by applicant]
US 10960009B2 · Vanover et al. · 2021 [cited by applicant]
US 10960010B2 · Vanover et al. · 2021 [cited by applicant]
US 10961245B2 · Li et al. · 2021 [cited by applicant]
US 11014925B2 · Li et al. · 2021 [cited by applicant]
US 11026951B2 · Vanover et al. · 2021 [cited by applicant]
US 11052083B2 · Li et al. · 2021 [cited by applicant]
US 11053245B2 · Mates et al. · 2021 [cited by applicant]
US 11066407B2 · Tomesch et al. · 2021 [cited by applicant]
US 11096944B2 · Yao et al. · 2021 [cited by applicant]
US 11124514B2 · Mates et al. · 2021 [cited by applicant]
US RE48839E · Mates et al. · 2021 [cited by applicant]
US 11311536B2 · Li et al. · 2022 [cited by applicant]
US 11331316B2 · Li et al. · 2022 [cited by applicant]
US 11376249B2 · Li et al. · 2022 [cited by applicant]
US 11407751B2 · Tomesch et al. · 2022 [cited by applicant]
US 11427587B2 · Li et al. · 2022 [cited by applicant]
US 11453670B2 · Li et al. · 2022 [cited by applicant]
US 11560382B2 · Mates et al. · 2023 [cited by applicant]
US 11680065B2 · Li et al. · 2023 [cited by applicant]
US 11723909B2 · Yao et al. · 2023 [cited by applicant]
US 11806347B2 · Li et al. · 2023 [cited by applicant]
US 11806348B2 · Li et al. · 2023 [cited by applicant]
US 11980617B2 · Snyder · 2024 [cited by applicant]
US 12090155B2 · Mates · 2024 [cited by applicant]
US 20040034015A1 · Robichaud et al. · 2004 [cited by applicant]
US 20040127482A1 · Robichaud et al. · 2004 [cited by applicant]
US 20040220178A1 · Robichaud et al. · 2004 [cited by applicant]
US 20060178362A1 · Robichaud et al. · 2006 [cited by applicant]
US 20110269777A1 · Bachurin et al. · 2011 [cited by applicant]
US 20140080816A1 · Koolman et al. · 2014 [cited by applicant]
US 20150374684A1 · Javitt et al. · 2015 [cited by applicant]
US 20190211015A1 · Mittelman et al. · 2019 [cited by applicant]
US 20190388418A1 · Li et al. · 2019 [cited by applicant]
US 20200087305A1 · Tomesch et al. · 2020 [cited by applicant]
US 20200102304A1 · Li et al. · 2020 [cited by applicant]
US 20200102309A1 · Li et al. · 2020 [cited by applicant]
US 20200148683A1 · Peddy et al. · 2020 [cited by applicant]
US 20200157100A1 · Li · 2020 [cited by applicant]
US 20200392135A1 · Wennogle et al. · 2020 [cited by applicant]
US 20200405713A1 · Mates et al. · 2020 [cited by applicant]
US 20200407362A1 · Mates et al. · 2020 [cited by applicant]
US 20210002280A1 · Mates et al. · 2021 [cited by applicant]
US 20210008065A1 · Li et al. · 2021 [cited by applicant]
US 20210009592A1 · Li et al. · 2021 [cited by applicant]
US 20210060009A1 · Synder et al. · 2021 [cited by applicant]
US 20210070755A1 · Berecz et al. · 2021 [cited by applicant]
US 20210315891A1 · Li et al. · 2021 [cited by applicant]
US 20220362241A1 · Davis et al. · 2022 [cited by applicant]
US 20230372336A1 · Dutheil et al. · 2023 [cited by applicant]
EP 1564671A1 · 2005 [cited by applicant]
WO 2000064899A1 · 2000 [cited by applicant]
WO 2000077001A1 · 2000 [cited by applicant]
WO 2000077002A1 · 2000 [cited by applicant]
WO 2000077010A2 · 2000 [cited by applicant]
WO 2003091250 · 2003 [cited by applicant]
WO 2008112280A1 · 2008 [cited by applicant]
WO 2017117514A1 · 2017 [cited by applicant]
WO 2018031535A1 · 2018 [cited by applicant]
WO 2018106916A1 · 2018 [cited by applicant]
WO 2019102240A1 · 2019 [cited by applicant]
WO 2021119334 · 2021 [cited by applicant]
McIntyre et al., “The Efficacy of Lumateperone in Patients with Bipolar Depression with Mixed Features,” J Clin Psychiatry, vol. 84, No. 3, 10 pages (2023). [cited by applicant]
McIntyre et al., “The Efficacy of Lumateperone on Symptoms of Depression in Bipolar I and Bipolar II Disorder: Secondary and Post Hoc Analyses,” European Neuropsychopharmacology, vol. 68, p. 78-88, (2023). [cited by applicant]
Newton, W., “Intra Intra-Cellular Reports Positive Phase III Trial of Caplyta in MDD and Bipolar Depression,” ClinicalTrials Arena, Mar. 29, 2023, retrieved from https://www.clinicaltrialsarena.com/news/news-intra-cellu… [cited by applicant]
Snyder, G. et al., “Functional Profile of a Novel Modulator of Serotonin, Dopamine, and Glutamate Neurotransmission,” Psychopharmacology, vol. 232, No. 3, 605-621, (2015); Published online Aug. 2014, DOI 10.1007/s00213-… [cited by applicant]
“Clinical Trial Evaluating ITI-007 (Lumateperone) as a Monotherapy for the Treatment of Bipolar,” ClinicalTrials.gov (Identifier: NCT02600494), 5 pages, (2015). [cited by applicant]
“Clinical Trial Evaluating ITI-007 as an Adjunctive Therapy to Lithium or Valproate for the Treatment of Bipolar Depression,” ClinicalTrials.gov, 6 pages, Nov. 9, 2015. [cited by applicant]
“Study of a Novel Antipsychotic ITI-007 in Schizophrenia,” Clinical Trials.gov, 6 pages, Dec. 26, 2011. [cited by applicant]
Aiken, C., “An Overview of Atypical Antipsychotics for Bipolar Depression,” published on Jan. 3, 2020 at https://www.psychiatrictimes.com/view/overview-atypical-antipsychotics-bipolar-depression, 11 pages. [cited by applicant]
Barman, R. et al., “Newer Antipsychotics: Brexpiprazole, Cariprazine, and Lumateperone: A Pledge or Another Unkept Promise?,” World J. Psychiatr., vol. 11, No. 12, pp. 1228-1238, (2021). [cited by applicant]
Bastin, R. et al., “Salt Selection and Optimized Procedures for Pharmaceutical New Chemical Entities,” Organic Process and Research Development, vol. 4, No. 5, pp. 427-435, (2000). [cited by applicant]
Calabrese, J. et al., “Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated with Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial,” American Journal of Psychiatry, … [cited by applicant]
Correll, C. et al., “Efficacy and Safety of Lumateperone for Treatment of Schizophrenia A Randomized Clinical Trial,” JAMA Psychiatry, vol. 77, No. 4, pp. 349-358, (2020). [cited by applicant]
Davis, R. et al., “ITI-007 demonstrates brain occupancy at serotonin 5-HT2A and dopamine D2 receptors and serotonin transporters using positron emission tomography in healthy volunteers,” Psychopharmacology, vol. 232, p… [cited by applicant]
Davis, R. et al., “ITI-007 in the treatment of schizophrenia: from novel pharmacology to clinical outcomes,” Expert Review of Neurotherapeutics, vol. 16, No. 6, pp. 601-614 (2016). [cited by applicant]
Davis, R. et al., “ITI-007: A Novel Treatment for Behavioral Disturbances Associated with Dementia and Related Disorders,” Clinical Trials in Alzheimer's Disease (CTAD) Congress 2014 (2014) (poster presentation). [cited by applicant]
Davis, R. et al., “Rationale for the Development of Low Doses of ITI-007 for the Treatment of Behavioral Disturbances Associated with Dementia,” The Journal of Prevention of Alzheimer's Disease, 2(4):302 (2015) (Clinica… [cited by applicant]
Davis, R. et al., “Lumateperone (ITI-007), A Novel Drug in Development for the Treatment of Agitation in Patients with Dementia, including Alzheimer's Disease: Rationale and Clinical Design,” The Journal of Prevention o… [cited by applicant]
Edinoff, A. et al., “Lumateperone for the Treatment of Schizophrenia,” Psychopharmacology Bulletin, vol. 50, No. 4, pp. 32-59, (2020). [cited by applicant]
Gramigna, J, “Lumateperone Safe, Effective for Depressive Symptoms Among Patients with Bipolar Disorders,” American Society of Clinical Psychopharmacology Annual Meeting, Jun. 2, 2020, 3 pages. [cited by applicant]
Hackam, D. et al., “Translation of Research Evidence from Animals to Humans,” JAMA, vol. 296, No. 14, pp. 1731-1732, (2006). [cited by applicant]
Harvey, P. et al., “Lumateperone Improves Negative Symptoms Related to Emotional Experience (Avolition) in Patient with Schizophrenia,” Abstract presented at the American Society of Clinical Psychopharmacology (ASCP) An… [cited by applicant]
Hlavinka, E., “Schizophrenia Tx Eases Depression in Bipolar Disorder: Lumateperone Offers Greater Rate of Response, Remission versus Placebo,” Medpage Today, 7 pages, (2020); https://www.medpagetoday.com/meetingcoverage… [cited by applicant]
Intra-Cellular Therapies, Inc., “Corporate Presentation” (Sep. 24, 2019), downloaded from https://ir.intracellulartherapies.com/static-files/93b08960-f01c-4864-aa22-8cadb3539753 (last accessed Mar. 13, 2023). [cited by applicant]
Kantrowitz, J., “The Potential Role of Lumateperone-Something Borrowed? Something New?,” JAMA Psychiatry, vol. 77, No. 4, pp. 343-344, (2020), Abstract only. [cited by applicant]
Kendrick, T., “The Newer, ‘Atypical’ Antipsychotic Drugs—Their Development and Current Therapeutic Use,” British J. General Practice, vol. 49, pp. 745-749, (1999). [cited by applicant]
Khorana, N. et al., “Gamma-Carbolines: Binding at 5-HT5A Serotonin Receptors,” Bioorganic & Medicinal Chemistry, vol. 11, D. 717-722, p. 718, Table 1, (2003). [cited by applicant]
Kumar, B. et al., “Lumateperone: A New Treatment Approach for Neuropsychiatric Disorders,” Drugs of Today, vol. 54, No. 12, pp. 713-719, (2018). [cited by applicant]
Lammers, L. et al., “Risperidone Long-acting Injection in Schizophrenia Spectrum Illnesses Compared to First Generation Depot Antipsychotics in an Outpatient Setting in Canada,” BMC Psychiatry, vol. 13, No. 155, 9 pages… [cited by applicant]
Lee, T. et al., “Novel, Highly Potent, Selective 5-HT2A/D2 Receptor Antagonists as Potential Atypical Antipsychotics,” Bioorganic & Medicinal Chemistry Letters, vol. 13, pp. 767-770, (2003). [cited by applicant]
Li, P. et al., “Discovery of a Tetracyclic Quinoxaline Derivative as a Potent and Orally Active Multifunctional Drug Candidate for the Treatment of Neuropsychiatric and Neurological Disorders,” Journal of Medicinal Chem… [cited by applicant]
Liebermann, J. et al., “ITI-007 for the Treatment of Schizophrenia: A 4-Week Randomized, Double-Blind, Controlled Trial,” Biological Psychiatry, vol. 79, pp. 952-961, (2016). [cited by applicant]
Makadia, H. et al., “Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier,” NIH Public Access, Authors Manuscript, available in PMC 2012, 19 pages, front page states: Published in final … [cited by applicant]
Marek, G. et al., “Synergistic Action of 5-HT2A Antagonists and Selective Serotonin Reuptake Inhibitors in Neuropsychiatric Disorder,” Neuropsychopharmacology, vol. 28, pp. 402-412, (2003). [cited by applicant]
McIntyre, R. et al., “Rapid-acting Antidepressants in Psychiatry: Psychedelics, Episodic Treatments, Innovation, and Clarion Call for Methodologic Rigor in Drug Development,” Expert Opinion on Drug Safety, vol. 21, No. … [cited by applicant]
O'Gorman, et al., “Lumateperone (ITI-007): A Novel Investigational Agent with Broad Therapeutic Potential Across Multiple Neuropsychiatric Disorders,” Poster P.1.g.038, European College of Neuropsychopharmacology (ECNP)… [cited by applicant]
Press Release, “Intra-Cellular Therapies Announces Additional Results From Phase I/II Clinical Trial for ITI-007 in Healthy Geriatric Subjects and Patients With Dementia,” Intra-Cellular Therapies, Press Release Date: N… [cited by applicant]
Press Release, “Intra-Cellular Therapies Announces Positive Top-Line Results from a Phase 3 Trial of Lumateperone in Patient with Bipolar Depression,” Intra-Cellular Therapies, Press Release Date: Jul. 8, 2019. [cited by applicant]
Press Release, “Intra-Cellular Therapies Announces Top-Line Results from the Second Phase 3 Trial of ITI-007 in Patients with Schizophrenia (Study '302)”, Intra-Cellular Therapies, Press Release Date: Sep. 28, 2016, 8 p… [cited by applicant]
Press Release, “Intra-Cellular Therapies Presents Data on Symptom Improvement by Lumateperone on Negative Symptoms, Depression, and Social Function in Patients with Schizophrenia at the American Society of Clinical Psyc… [cited by applicant]
Press Release, “Intra-Cellular Therapies Reports Positive Final Results of a Phase II Clinical Trial With ITI-007 in Patients with Sleep Maintenance Insomnia.”, Intra-Cellular Therapies, Press Release Date: Mar. 10, 200… [cited by applicant]
Pubchem, OPEN Chemistry Database, PubChem SID 103920954, PubChem CID 90655118, (2011), 6 pages. [cited by applicant]
Rainer, M., “Risperidone Long-acting Injection: A Review of its Long Term Safety and Efficacy,” Neuropsychiatric Disease and Treatment, vol. 4, No. 5, pp. 919-927, (2008). [cited by applicant]
Satlin, A. et al., “ITI-007 (Lumateperone) for the Treatment of Agitation in Patients with Dementia, including Alzheimer's Disease,” Alzheimer's & Dementia, vol. 14, No. 7, pp. 678-679, (2018), (Alzheimer's Assoc. Inter… [cited by applicant]
Satlin, A. et al., “ITI-007 (Lumateperone) for the Treatment of Agitation in Patients with Dementia, including Alzheimer's Disease,” Poster P2-032, Alzheimer's Assoc. International Conference 2018, (2018). [cited by applicant]
Tohen, M. et al., “Efficacy of Olanzapine and Olanzapine-Fluoxetine Combination in the Treatment of Bipolar I Depression,” Arch Gen Psychiatry, vol. 60, pp. 1079-1088, (2003). [cited by applicant]
Vanover, K. et al., “Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia,” Neuropsychopharmacology, vol. 44, pp. 598-605, (2019). [cited by applicant]
Vanover, K. et al., “ITI-007: A Novel Therapy for the Treatment of Schizophrenia and Related Psychoses,” International Clinical Psychopharamcology, vol. 26, e56, 1 page, (2011). [cited by applicant]
Vanover, K. et al., “A Novel Approach to Address an Unmet Need in the Treatment of Schizophrenia and Depression: Lumateperone, an Innovative Modulator of Dopamine, Serotonin, and Glutamate,” Abstract presented at the Am… [cited by applicant]
Vanover, K. et al., “Lumateperone (ITI-007): A Novel Investigational Agent with Broad Therapeutic Potential Across Multiple Neuropsychiatric Disorders,” European Neuropsychopharmacology, vol. 27, pp. S660-S661 (2017) (S… [cited by applicant]
Vanover, K. et al., Abstracts of the 13th International Congress on Schizophrenia (ICOSR) (Apr. 2-6, 2011), Schizophrenia Bull., vol. 37, Suppl. 1., p. 325, (2011). [cited by applicant]
Vyas, P. et al., “An Evaluation of Lumateperone Tosylate for the Treatment of Schizophrenia,” Expert Opinion on Pharmacotherapy, vol. 21, No. 2, pp. 139-145, (2020); https://doi.org/10.1080/14656566.2019.1695778. [cited by applicant]
Wang, S. et al., “Rapid-acting Antidepressants Targeting Modulation of the Glutamatergic System: Clinical and Preclinical Evidence and Mechanisms,” General Psychiatry, vol. 35, No. e100922, 6 pages, (2022). [cited by applicant]
Wennogle, L. et al., “Activation of NMDA and AMPA Receptors by Lumateperone (ITI-007): Implications for Antidepressant Activity,” Abstract presented at the 2017 Collegium Internationale Neuro-Psychopharmacologicum (CINP… [cited by applicant]
Witkin, J. et al., “Chapter 3: Rapid-acting Antidepressants,” Advances in Pharmacology, vol. 86, 50 pages, (2019). [cited by applicant]
“Guidance for Industry: Q3A Impurities in New Drug Substances,” U.S. Food & Drug Administration, Center for Drug Evaluation and Research, Jun. 2008 (last accessed Apr. 3, 2025) (available at https://www.fda.gov/media/71… [cited by applicant]
Defendants' Joint Initial Invalidity Contentions, Ex. E ('419 Patent), [cited by applicant]
Defendants' Joint Initial Invalidity Contentions, Ex. P ('792 Patent), [cited by applicant]
Hofmann et al., “Effect of Treatments for Depression on Quality of Life: A Meta-Analysis,” Cogn. Behav. Ther., vol. 46, No. 4, p. 265-286, (2017). [cited by applicant]
Press Release, “Intra-Cellular Therapies, Inc. Receives Exclusive License for Central Nervous System Compounds from Bristol-Myers Squibb Company,” Intra-Cellular Therapies, Inc. Press Release Date: Jun. 1, 2005. [cited by applicant]